Current understanding of the development of chronic back pain is rudimentary. In the last funding period our work focused on discovering brain-derived biomarkers typifying clinical chronic pain conditions. We uncovered a specific set of markers that not only distinguish chronic pain patients from healthy subjects, but also differentiate among various chronic pain conditions. In this next phase of study we intend to use these biomarkers to define - for the first time - temporal changes in brain physiology, anatomy, and metabolism that accompany the transition from sub-acute to chronic pain, and to distinguish predictive markers from those that are a consequence of the chronic pain. We will also identify which of these parameters reverse when the pain subsides, thereby determining if brain injury caused by chronic pain will be transient or permanent. In Aim 1, we longitudinally track brain morphology, brain physiology, and brain metabolic markers in subacute back pain patients for 18 months as they transition to either chronic pain or pain resolution. Changes in brain biomarkers are studied as a function of the final pain state (chronic vs. resolution) and of the time from subacute pain state. Hypotheses are advanced regarding changes in these markers based on our results in cross-sectional studies. In Aim 2, we build a predictive model for assessing one's risk for transitioning from subacute to chronic back pain based on the results of Aim 1. In this aim we pool the outcome measures and use them together for predicting transitions to chronic pain and to pain resolution, as well as for predicting the clinical characteristics of subacute and chronic pain. In Aim 3, we perform a cross-sectional case-control study to determine brain morphology, brain physiology, and brain metabolic markers in chronic back pain patients who have been in the condition for at least five years, and contrast these parameters to both the subacute population studied in Aim 1 and to matched healthy control subjects, in order to determine which parameters progress as chronic pain is sustained for several years. Our previous cross-sectional studies show that the brain plays a prominent role in chronic back pain. Here we test the involvement and causative role of brain biomarkers in the progression of back pain from a subacute to a chronic state. PUBLIC HEALTH RELEVANCE Chronic back pain is a major health problem and there is little understanding of its underlying mechanisms. We have shown that many brain properties are different in chronic back pain patients in contrast to healthy controls. Here we examine these brain biomarkers as we track subjects transitioning from subacute back pain to either pain resolution or to chronic pain, over an 18 month monitoring period, and contrast these outcomes to healthy controls and to more chronic back pain patients. We also plan to build models for predicting chronic pain based on brain parameters measured in the subacute stage. [unreadable] [unreadable] [unreadable]